MET Overexpression By IHC
What is MET overexpression?
MET overexpression means that cancer cells are producing an abnormally high amount of MET protein on their surface. Unlike MET exon 14 skipping or MET amplification — which are genetic alterations detectable by DNA sequencing — MET overexpression is a protein-level finding requiring a different kind of test.
How it’s detected: immunohistochemistry (IHC)
Immunohistochemistry (IHC) is a laboratory technique that uses antibodies to detect specific proteins in tumor tissue. A pathologist scores the staining result based on the intensity and percentage of tumor cells showing MET protein on their surface.
For Emrelis (telisotuzumab vedotin-tllv), the FDA-approved scoring system defines high MET overexpression as 50% or more of tumor cells showing strong (3+) staining. This is the threshold used in the LUMINOSITY trial that supported FDA approval in May 2025.
NGS alone will not find this.
MET overexpression is a protein biomarker, not a genomic one. Standard next-generation sequencing panels — including liquid biopsy — do not detect it. You need a separate IHC test ordered on tumor tissue. If you have not had MET IHC testing, ask your oncologist about it, especially if your cancer has progressed on prior therapy.
Why this matters now
In May 2025, the FDA granted accelerated approval to Emrelis (telisotuzumab vedotin-tllv) for adults with locally advanced or metastatic non-squamous NSCLC who have high c-MET protein overexpression and have received prior systemic therapy. MET overexpression is observed in up to 50% of patients with advanced NSCLC — and has historically been underdiagnosed because IHC testing was not routinely ordered.
What to ask your care team
Ask whether MET IHC testing was included in your workup. If not, ask whether a tissue sample is available for testing. Updated NCCN guidelines recommend testing for c-MET overexpression by IHC in patients with advanced or metastatic non-squamous NSCLC, alongside comprehensive genomic panel testing.
If you are already on treatment and your cancer has progressed, repeat MET IHC testing may be appropriate — c-MET expression can change over time and with prior therapy.